Objective To evaluate the proteetive effect of Valerian oil on lipid-induced nephropathy in Hypercholosterolemic rats and study its possible mechanisms.Methods SD rats were randomly divided into control group,hyperlipidemia group,low-dose[12.5mg/(kg·d)]valerian oil group,middle-dose[25mg/(kg·d)]valerian oil group,high-dose[(50me/(kg·d)]valerian 0il group and simvastatin group[5ms/(kg·d)for lavage].Dietary-induced hyperlipidemia were by given 4％cholosteml and 1％cholic acid diet for 16 weeks.Changes of serum lipid,urinary albumin,renal function and renal pathobiology index were assessed.The expression of integrin α3β1in glomeruli was detected by immunohistochemical stain,the expression of integrin ot3～l and TGF-β1 mRNA were detected by RT-PCR at the same time.Results The serum levels of total cholesterol,low density lipopmtein and seruln creatinine in Valerian group and simvastatin group were decreased more than that in hypedipidemia group.Urinary albumin excretion Was significantly reduced。in Valerian group after treatment for 8 weeks,and significantly reduced in simvaatatin group after 16 weeks.The morphological analysis revealed that the pathobiology index in Valerian group were significantly decreased than that in simvastatin group after 16 weeks.At the sanle time,the expression of integrin α3β1 mRNA and protein in Valerian group were significantly increased than that in hyperlipidemia group and simvastatin group,and the expression of TGF-β1mRNA were markedly decreased in Valerian group.The treatment effect in Valerian group Wag better than that insimvaatatin group.Conclusion Valerian oil has the protective effects on lipid-induced nephropathy by decreasing serum lipid,increasing the expression of integrin α3β1 and inhibiting the expression of TGF-β1.The protective effects of Valerian oil ale better than simvastatin.

Objective To explore the expression and significance of nestin in renal tubular epithelial cells in hypercholesterolemic rats. Methods Dietary-induced hyperlipidemia were induced in female SD rats by given 4% cholesterol and 1% cholic acid diet for 16 weeks. Changes of serum lipid, urinary albumin, serum creatinine and renal interstitial pathological changes were assessed. The expression of nestin and a-smooth muscle actin (α-SMA) were detected by immunohistochemical stain. Results The serum levels of total cholesterol, low density lipoprotein, urinary albumin and serum creatinine were significantly increased in hyperlipidemia group, accompanied with renal interstitial injury and fibrosis. As time extended, the expression of nestin and a-SMA in renal tubular epithelial cells were increased significantly. There was positive correlation among the expression of nestin and total cholesterol, low density lipoprotein, urinary albumin and serum creatinine( r =0.963,0.830,0.944,0.706, P <0.01). Nestin also had a positive correlation with tubular-interstitial index ( r = 0. 974, P < 0. 01) and α-SMA ( r = 0. 804, P < 0. 01). Conclusion The increased expression of nestin may be associated with renal tubular-interstitial fibrosis and tubular epithelial myofibroblast transdifferentiation in hypercholesterolemic rats.

Objective To investigate the effect of artorvastatin on macrophage accumulation in tubulointerstitium of unilateral ureteral obstructive (UUO) nephropathy and its possible mechanism.Methods Twenty-one rats were randomly divided into three groups: sham-operatipn, UUO, UUO+ artorvastatin. Immunohistochemistry staining of CD68 and M-CSF was used to define the macrophage accumulation and expression of interstitial M-CSF. Lipid profile in these groups was also determined. Results CD68 + cells and M-CSF expression were significantly increased at day 10 after UUO operation, this kind of CD68 + cell accumulation and M-CSF expression up-regulation were ameliorated by artorvastatin treatment. In UUO and atorvastatin treated groups, the number of macrophage was positively correlated with tubulointerstitial M-CSF expression. There was no significant difference about serum lipid among the three groups. Conclusion Atorvastatin can reduce interstitial macrophage accumulation in UUO nephropathy. This therapeutic effect might relate to down-regulation of tubulointerstitial M-CSF expression.

Objective To observe the renal expression of cyclooxygenase-2 (COX-2) in rats with type 2 diabetes, and explore the effect of selective COX-2 inhibitor Mobic on the expression of renal COX-2, matrix metalloproteinase-9(MMP-9), tissue inhibitor of matrix metalloproteinase-1(TIMP-1), TXB 2 and 6-Ket-PGF1?, as well as renal structure and function. Methods All rats were divided into control group, diabetes mellitus group and treatment group. Type 2 diabetic rats were treated with Mobic and vehicle respectively. Immunohistochemistry was used to detect the expression of COX-2,MMP-9 and TIMP-1 in renal tissues. The urinary TXB 2 and 6-Ket-PGF1? concentration was determined by radioimmunoassay at 6th week. Results There were an increasing expression of COX-2, TIMP-1 and decreasing MMP-9 expression in the renal tissue of type 2 diabetic rats. Mobic could increase MMP-9 expression and depress TIMP-1 expression througth inhibiting the expression of COX-2 in the renal tissues of type 2 diabetic rats. Conclusion COX-2 was involved in the pathogenesis of type 2 diabetic nephropathy. Selective COX-2 inhibitor Mobic might exert its renoprotective effects through inhibiting COX-2 activity, decreasing prostagladins systhesis, and modulating MMP-9 and TIMP-1 expression.

Objective To investigate the change of erythrocyte immune function and T lymphocyte subsets in patients with uremia and the effect of hemodialysis on them. Methods Flow cytometry and immune adherence rosette method were used to measure the activity of RBC-CR1and the changes of T lymphocyte subsets in 23 uremic patients without hemodialysis, 22 uremic patients before and after sigle hemodialysis and 21 healthy subjects as the control group. Results The activity of RBC-CR1, the number of T lymphocyte subsets significantly changed in patients with uremia, and hemodialysis could partially improve this condition. There was obvious correlation between erythrocyte immune function and T lymphocyte subsets. Serum creatinine was positively relative to the value of RBC-C 3b RR(P

Objective To develop a rat model of type 2 diabetes, and to investigate the effect of AT1 receptor antagonist-irbesartan on activation of renal NF-?B in type 2 diabetic rat. Methods The rats of model groups were intraperitoneally given low-dose streptozotocin (STZ, 30 mg/kg) after having the sucrose-and fat-enriched diets(20% sucrose, 10% pig fat, 2. 5% cholesterol) for one month. Immuohistochemistry and computer image-pattern analysis system were used to analyze activation of NF-?B and expression of monocyte/macrophage (ED-1) in renal tissues. Results (1) Insulin resistance was induced by feeding diets enriched in sucrose and fat, and hyperglycemia was induced with a dose of STZ that did not cause diabetes in chow-fed rats. After 6 weeks, rats of model group presented itself early changes of diabetic nephropathy (DN). (2) Compared to normal group, the activation of NF-?B and expression of ED-1 increased in glomeruli of experimental type 2 diabetic rat. Irbesartan inhibited significantly the activation of NF-?B, ameliorated monocyte/macrophage infiltration, partly improved the renal function and matrix accumulation. Conclusions (1) A rat model of type 2 diabetes mellitus is developed successfully by combination of dietary-induced insulin resistance and low-dose STZ-induced hyperglycemia. (2) Renal NF-?B activation is greatly increased in experimental type 2 diabetic rat. The protection of irbesartan against kidney is associated, at least in part, with down-regulating NF-?B activation and monocyte/macrophage recruitment in renal tissue.

Objective To investigate the renoprotective effect of irbesartan on tubulointerstitial fibrosis in rats with adriamycin-induced nephropathy and its possible mechanism. Methods Rats received twice-intravenous injections of adriamycin(ADR) after the right kidney was removed. Those rats were randomly assigned to irbesartan treatment group and nephropathy group. Treatment group received 50 mg? kg-1 ? d-1 irbesartan for 4 weeks. Rats with sham operation served as normal control. Proteinuria and serum creatinine of were measured after 4 weeks. Renal histopathological changes were evaluated as well. Immunohistochemistry was used to examine the protein expression of TGF-?1, MMP-9 and TIMP-1. The mRNA levels of MMP-9 and TIMP-1 were detected by in situ hybridization. Results Proteinuria of treatment group decreased significantly as compared to nephropathy group. TGF-?1, TIMP-1 and MMP-9 were significantly lower than that of nephropathy group in tubulointerstitium and consistently associated with tubular degeneration and interstitial fibrosis progressed. Conclusion Irbesartan has a renoprotective effect on tubulointerstitial fibrosis by modulating the ECM degradation.

Objective To investigate the effect of fluvastatin on activation of nuclear factor kappa B (NF-κB)induced by angiotensin Ⅱ (Ang Ⅱ ) in rat kidney tubular epithelial cells (NRK-52E). Methods NRK-52E cells were divided into (1)control group ; (2)Ang Ⅱ groups with different concentration and time; (3)Ang Ⅱ (10-6 mol/L)+SB203580 ( 10 μmol/L)group; (4) Ang Ⅱ (10-6mol/L) +different fluvastatin concentration (10-7, 10-6, 10-5 mol/L)groups;(5)Ang Ⅱ (10-6mol/L) +fluvastatin (10-5 mol/L) +mevalonate (10-4 mol/L)groap. Electrophoretic mobility shift assays (EMSA) was used to detect NF-κB activation. Phosphorylation of cellular p38 mitogen-activated protein kinase (p38MAPK) was determined by Western blot. Monocyte chemoattractant protein (MCP)-1 mRNA was determined by RT-PCR. Results Ang Ⅱ stimulated the DNA-binding activity of NF-κB,phosphorylation of p38MAPK and up-regulated the expression of MCP-1mRNA in cultured NRK-52E cells in a dose-dependent manner (P<0.01). Ang Ⅱ (10-6 mol/L) induced a rapid (5 minutes) elevation of the p38MAPK phosphorylation. NF-κB DNA binding activity was increased at as early as 30 minutes(P<0.01), peaked at 2 hours after AngⅡ treatment (P<0.01). This stimulatory effect of Ang Ⅱ on NF-κB was blocked by SB203580 (a specific inhibitor of p38MAPK) (P<0.01). Incubation of cells with fluvastatin significantly inhibited the Ang Ⅱ-induced NF-κB activation and expression of MCP-1 mRNA in dose-dependent manner (P< 0.05). Exogenous mevalonate (10-4 mol/L) prevented the effect of fluvastatin on NF-κB activation (P <0.05). Conclusions Fluvastatin reduces Ang Ⅱ-induced NF-κB activation via the p38MAPK pathway in NRK-52E cells. Such effect of flurastatin is partly through blocked by mevalonate.

Objective To investigate the effects and underlying mechanism of the scavenger receptor CD36 in high glucose-induced rat glomerular mesangial cells apoptosis.Methods The mesangial cells of rats were divided into 4 groups:control group (5.6 mmol/L glucose),mannitol group (24.2 mmol/L mannitol+5.6 mmo]/L glucose),high glucose group (30 mmol/L glucose),CD36 monoantibody group (30 mmol/L glucose+CD36 mono-antibody).The intracellular ROS level was detected by confocal microscopy with fluorescent probe CM-H2DCFDA.MDA,GSH-PX,8-OHDGA in cell supernatant were detected.Apoptosis was determined by flow cytometry followed by Annexin V-FITC/PI double stains.The expression of CD36,Bax and Bcl-2 were detected by RT-PCR and Western blotting.Results The expression of CD36 was detected in glomerular mesangial cells.The highest level was found in high glucose group in 24 hours.There was no significant difference found between control group and mannitol group with respect to intracellular ROS generation,MDA,8-OHDG,GSH-PX level,apoptosis rate,expression of CD36,Bax and Bcl-2 (all P ＞ 0.05).There was no significant difference in the expression of CD36 between CD36 mono-antibody group and high glucose group (P ＞ 0.05).Compared to control group,the intracellular ROS generation,MDA and 8-OHDG levels,apoptosis rate,the expression of CD36 and Bax were significantly increased,the GSH-PX level and the expression of Bcl-2 were significantly lower in high glucose group (all P ＜ 0.05).Compared to the high glucose group,the intracellular ROS generation,MDA and 8-OHDG levels,apoptosis rate,the expression of Bax were suppressed but the GSH-PX level and the expression of Bcl-2 increased in CD36 mono-antibody group (all P ＜ 0.05).The intracellular ROS level was positively correlated with apoptosis rate,protein expression of CD36 and Bax gene,was negatively correlated with Bcl-2 protein expression.Conclusions CD36 was involved in the high glucose induced apoptosis of mesangial cells which was potentially mediated by an increased level of oxidative stress.

Objective To investigate the renoprotective effect of erythropoietin(EPO) in streptozotocin-induced diabetic rats and to explore the possible mechanism.Methods The SD rats were randomly divided into there groups: normal control rats, diabetic, diabetic treated with EPO(NC, DM, DE groups).The rats were sacrificed after 8 weeks treatment.Renal morphology was observed by light microscopy.The expression of erythropoietin receptor(EPOR) in kidney was detected by immunofluorescence and Western blotting.The expression of p47phox, transforming growthfactor (TGF)β1andfibronectin (FN)proteininkidneywasdetectedby immunohistochemistry and Western blotting.The activity of antioxidants including total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde(MDA) in kidney were also measured.Results EPO treatment notably attenuated renal pathologic and functional changes.The expression of EPOR was found in kidney,but there was no difference among groups(P＞0.05).Compared with normal rats, diabetic rats showed an elevated expression of p47phox, TGF-β1, FN proteins and MDA levels in kidney as well as reduced activities of SOD, GSH-Px and T-AOC (all P＜0.01).Compared with diabetic rats, EPO could decrease the protein expression of p47phox,TGF-β1and FN in kidney (all P＜0.05).Meanwhile, elevated MDA level in the kidney was decreased as well as decreased SOD, GSH-Px,T-AOC activities were significantly remitted in DE group(all P＜0.01).Conclusion EPO can amelioraterenaldamagevia theinhibition of oxidativestressandTGF-β1andFNprotein expression in streptozotocin-induced diabetic rats.